The development of safe, effective and acceptable microbicides is imperative in the fight against HIV/AIDS. The success of microbicide products will derive from the synergy of their biological functionality and user acceptability. Biological functionality is the integrated result of safe and effective anti-HIV compounds incorporated into formulations or devices that successfully deliver those compounds to target tissues, fluids and pathogens. Acceptability is a multi-factorial phenomenon that accounts for the personal, dyadic, productrelated and social contexts that potentiate - or not - a woman's decision to use a microbicide. Acceptability depends strongly upon delivery systems with biophysical functions and /or mechanical and materials properties that are most conducive to human use. Without both, microbicides' potential to impact the public health crisis of HIV/AIDS will be largely limited. Project 3 will integrate and extend our growing knowledge and methodologies in preclinical microbicide formulation and delivery device sciences, with their counterpart in early human studies of acceptability. It will extend current behavioral strategies for studying gel acceptability in preclinical frameworks, and expand those strategies to intravaginal ring (IVR) applications. Project 3 will first modify existing behavioral tools that measure topical gel acceptability dimensions for preclinical formulation development; the new tools will incorporate expanded acceptability dimensions to account for the use of long-acting gels and IVR devices developed in this U19. We will then extend our current preclinical in vivo human studies methodology, integrating imaging experiments with behavioral assessment. This will enable joint determination of two critical components of microbicide success: user acceptability and gel functionality. Further, we will use the expanded measures to analyze the correspondence between behavioral measures and biophysical measures, creating a statistical framework enabling prediction of user ratings of long-acting gel experiences from gel performance measures. Finally, we will examine user ratings of acceptability dimensions associated with these delivery systems, and propose initial preclinical standards of acceptability for long-acting gels and IVRs.